Uso de oligonucleotídeos para a tratamento da distrofia muscular em um modelo de camundongo severamente afetado

Inglaterra - os autores utilizaram os oligonucleotídeos por via sistêmica em camundongos com ausência de distrofina/utrofina; este camundongo tem fraqueza muscular e alterações da coluna, com sintomas muito severos. Neste experimento o tratamento melhorou todos os músculos exceto o coração. Os animais ficaram com características de camundongos normais como pode ser visto no vídeo.

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O resumo em inglês do trabalho pode ser lido abaixo:

(Mol.Ther, 2009) Prevention of Dystrophic Pathology in Severely Affected Dystrophin/Utrophin-deficient Mice by Morpholino-oligomer-mediated Exon-skipping

Aurélie Goyenvalle1, Arran Babbs1, Dave Powell1, Ryszard Kole2, Sue Fletcher3, Steve D Wilton3 and Kay E Davies1
1MRC Functional Genomics Unit, Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK;
2AVI Biopharma, Corvallis, Oregon, USA;
3Center for Neuromuscular and Neurological Disorders, University of Western Australia, Perth, Western Australia,

Duchenne muscular dystrophy (DMD) is a severe neuromuscular disorder caused by mutations in the dystrophin gene that result in the absence of functional protein. Antisense-mediated exon-skipping is one of the most promising approaches for the treatment of DMD because of its capacity to correct the reading frame and restore dystrophin expression, which has been demonstrated in vitro and in vivo. In particular, peptide-conjugated phosphorodiamidate morpholino oligomers (PPMOs) have recently been shown to induce widespread high levels of dystrophin expression in the mdx mouse model. Here, we report the effciency of the PPMO-mediated exon-skipping approach in the utrophin/dystrophin double-knockout mouse (dKO) mouse, which is a much more severe and progressive mouse model of DMD. Repeated intraperitoneal (i.p.) injections of a PPMO targeted to exon 23 of dystrophin pre-mRNA in dKO mice induce a near-normal level of dystrophin expression in all muscles examined, except for the cardiac muscle, resulting in a considerable improvement of their muscle function and dystrophic pathology. These fndings suggest great potential for PPMOs in systemic treatment of the DMD phenotype.

Fonte: http://distrofiamuscular.net/noticias.htm